Primary treatment of propionic acidemia complicated by acute thiamine deficiency.

Propionic acidemia is often manifested during the neonatal period with vomiting, failure to thrive, lethargy, and hyperammonemic coma when catabolism is prolonged. Mild lactic acidosis frequently accompanies metabolic decompensation. We present two patients with propionic acidemia whose initial manifestation was complicated by severe lactic acidosis caused by thiamine deficiency, which resulted from an inadequate supply of, and an increased need for, thiamine during metabolic stress. To prevent acute thiamine deficiency, we propose early vitamin supplementation during treatment of any severe metabolic decompensation accompanied by insufficient food intake.

Dyslipidaemia in a boy with recurrent abdominal pain, hypersalivation and decreased lipoprotein lipase activity.

UNLABELLED: An 8-year-old boy with frequently recurring pancreatitis-like abdominal pain, Fredrickson type V dyslipidaemia, and significantly decreased post-heparin plasma lipoprotein lipase (LPL) activity is described. In order to exclude familial LPL deficiency, the complete LPL coding gene sequence was analysed revealing compound heterozygosity for two mutations (Asp9Asn, Ser447Ter) which are not supposed to considerably impair lipolytic enzyme activity. However, until now the combination of both these mutations in one patient has not been observed. In addition to the common symptoms of LPL deficiency, a striking feature of unknown origin was hypersalivation. Treatment including a fat-restricted diet, omega-3 fatty acids, and nicotinic acid led to long symptoms-free intervals. Symptoms recurred however when the diet was not strictly adhered to. CONCLUSION: LPL deficiency is a rare cause of abdominal pain in childhood and deserves careful treatment in order to avoid pancreatitis. The presented patients is a unique compound heterozygote for two mutations which do not abolish lipolytic activity in the homozygote state. Identification of other individuals with this genotype is necessary to understand the phenotype in our patient.

Isolated biotin-resistant 3-methylcrotonyl-CoA carboxylase deficiency: long-term outcome in a case with neonatal onset.

UNLABELLED: A patient with early-onset 3-methylcrotonyl coenzyme A carboxylase (MCC) deficiency showing a severe clinical course is described. Abnormal eye and head movements suggestive of seizures were noticed soon after birth. Tonic convulsions at the age of 10 weeks led to admission. Urinary organic acid analysis using gas chromatography-mass spectrometry at 3 months of age revealed elevated concentrations of 3-hydroxyisovaleric acid (3HIVA) and 3-methylcrotonylglycine but normal levels of lactate, 3-hydroxypropionate and methylcitrate suggesting isolated MCC deficiency. This was confirmed by enzyme assays in lymphocytes and cultured skin fibroblasts: MCC activity was virtually undetectable whereas activities of propionyl-CoA and pyruvate carboxylases were within the normal range. A low protein (0.8-1.5 g/kg/day) diet supplemented with a leucine-free amino acid mixture resulted in a marked decrease of 3HIVA excretion. L-Carnitine and biotin administration had no effect on the clinical condition or metabolite excretion. Supplementation with glycine resulted in only a temporary fall of 3HIVA excretion and was therefore discontinued. L-Carnitine therapy was reintroduced later because of secondary carnitine deficiency. Compliance with treatment was poor until the age of 27 months resulting in a severe episode with seizures and coma. The general clinical condition of the patient was always good but his psychomotor development was delayed and seizures were not continuously under good control due to poor therapy compliance. The boy is now 10.5 years old and attending a school for children with learning handicaps. CONCLUSION: Isolated MCC deficiency of early-onset is a rare condition exhibiting a more severe clinical course than the later-onset form described in most other cases. The prognostic value of 3 HIVA measurements in CSF and serum should be evaluated in future cases.

Late form of vitamin K deficiency bleeding in Germany.

BACKGROUND: The evaluation of the disease of vitamin K deficiency bleeding (VKDB). METHOD: 108 reported cases between 1980 and 1990 from Germany. RESULTS: VKDB occurs preferentially (90%) in fully breastfed infants, males are affected nearly twice as often as females. The peak age is four weeks; the majority (79%) of the infants are between three and seven weeks old. 58% of the patients suffer from intracranial bleeding, which results in a total mortality rate of 19% and in neurological damage in 21%. Generally the VKDB occurred suddenly as no warning signs were noticed or they were so insignificant as not to be heeded. In at least 37% of the patients cholestasis was detected. The Quick value was pathologically low in every case. Vitamin K dependent factors were low and PIVKA was detectable, whereas vitamin K independent hemostatic parameters were normal or even elevated. The combination of low Quick value and normal fibrinogen as well as platelet level is a good diagnostic indicator which can be confirmed by administration of vitamin K, after which the Quick value will rise within 30 minutes. Vitamin K prophylaxis reduces the incidence of VKDB from 5.13 per 100,000 births to a tenth of that; single dose oral prophylaxis reduces the risk by a factor of 3.3 and a single parenteral dose by 14.3. Parenteral prophylaxis is more effective in patients with hepatobiliary disorders. Patients who suffered VKDB despite having received vitamin K prophylaxis are older at onset (without prophylaxis 32 days, with oral prophylaxis 37 days, and with parenteral prophylaxis 63 days) and have less intracranial bleeding (35%) than patients who received none (62%). CONCLUSION: Late form of VKDB is a rare but serious disease which can be prevented by VK-prophylaxis.

Origin of the left coronary artery from the right pulmonary artery and ventricular septal defect in a child of a mother with raised plasma phenylalanine concentrations throughout pregnancy.

A child with anomalous origin of the left coronary artery from the right pulmonary artery, ventricular septal defect, fetal growth retardation, and facial abnormalities was born to a woman in whom plasma phenylalanine concentrations had been raised throughout pregnancy. The cardiac abnormalities were diagnosed by angiography when the child was eight months old. The anomalous coronary artery was imaged in a subsequent echocardiogram. Development retardation was caused by maternal phenylketonuria, which may also have been responsible for the development of the ventricular septal defect and the coronary anomaly. If dietary treatment of the mother had been started before pregnancy damage to the child might have been prevented.

[Rothmund syndrome or Thomson syndrome. An analysis of the literature exemplified by a personal case]. / Rothmund-Syndrom oder Thomson-Syndrom. Eine kritische Analyse der Literatur am Beispiel eines eigenen Falles.

We report on a now 16 month old child, born with multiple bone defects. A characteristic poikiloderma leading to the diagnosis appeared after six months. A review of the literature is given and the clinical heterogeneity of the Rothmund-Thomson-Syndrome is discussed. It is suggested, that the combination of the described malformations represents a Thomson Syndrome.

Life-span and Menkes kinky hair syndrome: report of a 13-year course of this disease.

The life-span of Menkes syndrome patients is discussed in connection with a boy suffering from this disease who lived to the age of 13.5 years. The copper metabolism defect is described. Therapeutic trials, mainly copper substitution, and prospects are summed up.

[Embryofetopathy caused by postnatally detected maternal phenylketonuria]. / Embryofetopathie infolge einer postnatal erkannten maternalen Phenylketonurie.

A case of a now 10-month-old female infant is reported, who presented at birth with microcephalus, growth retardation, dystrophia, facial dysplasia and cardiac defect. Etiologically a classical phenylketonuria of the mother with very high levels of serum phenylalanine (51 and 41 mg/dl, respectively), which was not known until then, was diagnosed already after her confinement. The mother, aged 26, originates from Roumania. She had never been treated by any phenylalanine-limited diet. Psychological testing revealed a severely reduced intelligence (IQ = 63). The child, having normal levels of serum phenylalanine, presented with mild statomotor retardation at the age of ten months. Even in countries with a general neonatal screening program, a hitherto undiagnosed maternal phenylketonuria has to be considered within the differential diagnosis of a dystrophic microcephalic newborn, beside more common causes like the fetal alcohol syndrome.

[Need for the determination of chloramphenicol levels in the treatment of bacterial-purulent meningitis with chloramphenicol succinate in infants and small children]. / Die Notwendigkeit von Chloramphenicol-Spiegelbestimmungen während der Behandlung bakteriell-eitriger Meningitiden bei Säuglingen und Kleinkindern mit Chloramphenicol-Succinat.

17 cases of purulent meningitis in 15 children, aged 1 day to 5 years (median 8 months) were treated with continuous i.v. infusion of chloramphenicol succinate. Free chloramphenicol in serum and cerebrospinal fluid (C.F.) was assayed by high performance liquid chromatography (HPLC). CF chloramphenicol levels averaged 45 +/- 14% of the serum level. Out of 16 patients only five received the usually recommended dosage. In three others because of initially or progressively high serum levels the dose had to be diminished. In eight others because of subtherapeutic levels the dose had to be raised. The highest dose (390 mg/kg body weight/d) was required in a 2 month old boy. He was shown to have a clearance rate for free chloramphenicol considerably higher than has been reported so far. Maturation of the metabolism could be observed in a small-for-date newborn who acquired a grey baby syndrome during the treatment of his first meningitis. Several weeks later he required exactly the recommended dose to reach therapeutic chloramphenicol levels. As a consequence of these observations we strongly recommend meticulous drug monitoring of chloramphenicol in order to meet the large biological variations seen particularly in neonates and young infants in their capacity to reach and maintain therapeutic serum levels.

[Physiology of hemostasis in newborn infants. I]. / Physiologie der Hämostase der Neugeborenen. Teil I.

Ever since neonatal hemostasis has been studied systematically, a great number of single data und laboratory parameters have been collected which all differ more or less distinctly from results gained in adults. This has been leading repeatedly to the conclusion that the hemostasis in newborns is still immature or somehow insufficient. At least in healthy and term infants this does not apply; each pre- and postnatal stage of development has its own optimally functioning hemostasis changing with age due to respective physiological peculiarities which nevertheless may gain considerable pathogenetic significance for preterm or sick newborns. A good example are for instance the vascular structures of the periventricular germinal matrix in prematures born during the critical period around the 24th and 34th week of gestation. This assumption being in agreement with an important principle of developmental physiology is proven in this paper particularly for platelets and plasmatic coagulation.

[Pathology of hemostasis in newborn infants. II]. / Pathologie der Hämostase der Neugeborenen. Teil II.

Already in newborns almost all congenital and acquired disorders of hemostasis can be encountered. Especially gestational age and developmental peculiarities of hemostasis influence the incidence of the different causes for hemorrhages. Due to laboratory progress the well-known question of vitamin K deficiency and related bleeding has again become a point of interest and can be answered more clearly now than some years ago. Other significant disturbances of neonatal hemostasis are disseminated intravascular coagulation, intracranial hemorrhages, and the thrombocytopenias of the newborn. Disseminated intravascular coagulation is a pathogenetically important and frequent complication of numerous diseases in term as well as particularly in preterm infants. Ultrasonography gave new information about frequency and prognosis of intracranial hemorrhages in affected newborns. Finally, qualitative and quantitative disorders of the platelets present always a true challenge for the neonatologist in terms of differential diagnosis and differential therapy.

[Transient erythroblastopenia]. / Passagere Erythroblastopenie.

5 patients 10 to 20 months old with severe normochromic, normocytic anemia and reticulocytopenia are reported. All patients recovered within 10 days to 5 weeks. No steroid therapy was given. Failure to recognize the clinical entity leads to unnecessary diagnostic and therapeutic procedures including the transfusion of blood.

Seven years of experience with selective screening for organic acidurias.

Between 1975 and 1981 nearly 9000 patients with suspected inherited metabolic diseases were investigated by a selective screening procedure including, apart from simple tests for ketone bodies, sugars and SH-containing compounds, high voltage electrophoresis of amino acids as well as gas liquid chromatography and gas liquid chromatography-mass spectrometry of the organic acids. Fifty-two cases with 18 different inborn errors of metabolism were detected. The effectivity index was calculated to be 0.6% or 1 case in about 170 requests. From the presented and from already existing data in the literature the overall incidences for all organic acidurias together and for propionic acidemia separately were appraised to be 1:10000 and 1:50000, respectively. About half of the patients diagnosed by this screening may benefit from the diagnosis.

Analgesics during pregnancy.

The thalidomide tragedy of the late 1950s clearly proved the need for caution, and questionable drug use should always be avoided. The teratogenic potential of a drug is related to dosage and time of administration. During blastogenesis, fetal death may occur; during embryogenesis, deformity may develop; and during the last trimester, functional anomalies or "covert embryopathy" may be seen. Finally, the benefit to risk ratio of every drug must be carefully weighed, and only those with proved safety to the feto-maternal unit should be prescribed. Aspirin may be administered to the pregnant woman as an anti-inflammatory agent but in the lowest therapeutic dosage. In the later stages of pregnancy, however, aspirin should be avoided since it may prolong labor, lead to greater blood loss during delivery, and increase the incidence of stillbirths. The pyrazolones, although not associated with teratogenic side effects, may lead to sometimes fatal agranulocytosis and, accordingly, are not recommended in pregnancy. Acetaminophen is the analgesic and antipyretic of choice during all phases of pregnancy.