Carpal tunnel syndrome and finger deformities in children with mucopolysaccharidoses and mucolipidoses: a retrospective review of 52 patients.

This single-centre retrospective study reports our management of carpal tunnel syndrome in 52 children (103 hands) with mucopolysaccharidoses and mucolipidoses. All except one were bilateral. The median age at surgery was 4 years (range 1.5 to 12). The diagnosis of carpal tunnel syndrome was confirmed by an electromyogram (EMG) in all patients; 38% of these presented without any clinical signs. Surgical neurolysis was performed in all hands, combined with epineurotomy in 52 hands (50%) and flexor tenosynovectomy in 75 hands (73%). Surgery was bilateral in 98% of children (102 hands). The mean follow-up was 12 years (range 1 to 19) and the EMG was normalized in 78% of hands. Ten patients suffered recurrence, eight of whom required further surgery. Screening for carpal tunnel syndrome is essential for the management of children mucopolysaccharidoses and mucolipidoses. Surgical treatment should be carried out early with follow-up by EMG to detect recurrence.Level of evidence: IV.

Airway management and perioperative adverse events in children with mucopolysaccharidoses and mucolipidoses: A retrospective cohort study.

BACKGROUND: Children suffering from mucopolysaccharidoses (subtypes I, II, III, IV, VI, and VII) or mucolipidoses often require anesthesia, but are at high risk for perioperative adverse events. However, the impact of the disease subtype and the standard of care for airway management are still unclear. AIMS: This study aimed to assess independent risk factors for perioperative adverse events in individuals with mucopolysaccharidoses/mucolipidoses and to analyze the interaction with the primary airway technique implemented. METHODS: This retrospective study included individuals with mucopolysaccharidoses/mucolipidoses who underwent anesthesia at two high-volume centers from 2002 to 2016. The data were analyzed in a multivariate hierarchical model, accounting for repeated anesthesia procedures within the same patient and for multiple events within a single anesthesia. RESULTS: Of 141 identified inpatients, 67 (63 mucopolysaccharidoses and 4 mucolipidoses) underwent 269 anesthesia procedures (study cases) for 353 surgical or diagnostic interventions. At least one perioperative adverse event occurred in 25.6% of the cases. The risk for perioperative adverse events was higher in mucopolysaccharidoses type I (OR 8.0 [1.5-42.7]; P = .014) or type II (OR 8.8 [1.3-58.6]; P = .025) than in type III. Fiberoptic intubation through a supraglottic airway was associated with the lowest risk for perioperative adverse events and lowest conversion rate. Direct laryngoscopy was associated with a significantly higher risk for airway management problems than indirect techniques (estimated event rates 47.8% vs 10.1%, OR 24.05 [5.20-111.24]; P < .001). The risk for respiratory adverse events was significantly higher for supraglottic airway (22.6%; OR 31.53 [2.79-355.88]; P = .001) and direct laryngoscopy (14.8%; OR 14.70 [1.32-163.44]; P = .029) than for fiberoptic intubation through a supraglottic airway (2.1%). CONCLUSIONS: The disease subtype and primary airway technique were the most important independent risk factors for perioperative adverse events. Our findings indicate that in MPS/ML children with predicted difficult airway indirect techniques should be favored for the first tracheal intubation attempt.

Microvillus inclusion disease: a subtotal enterectomy as a bridge to transplantation.

BACKGROUND: Microvillus inclusion disease (MVID) is a known congenital cause of intractable diarrhea resulting in permanent intestinal failure. There is need for a lifelong total parenteral nutrition (TPN) from diagnosis and the prognosis is poor. Most patients die by the second decade of life as a result of complications of parenteral alimentation including liver failure or sepsis. The only available treatment at this moment is a small bowel transplantation. But before that moment, the patients often suffer from a persistent failure to thrive and electrolyte disturbances despite continuous TPN. METHODS AND RESULTS: We report what we believe is a first case of an extensive small bowel resection in a 5-month-old boy with proven MVID to act as a bridge to (liver-) intestinal transplantation to treat failure to thrive and intractable diarrhea. CONCLUSIONS: An extensive small bowel resection can be done to enhance the chance of survival leading up to the transplantation by managing fluid and electrolyte imbalance. It facilitates medical management of these patients and makes a bowel transplantation possible at a later stage.

[Intestinal failure and transplantation in microvillous inclusion disease]. / Fracaso intestinal y trasplante en la enfermedad por inclusiones microvellositarias.

INTRODUCTION: Microvillous inclusion disease is a rare autosomal recessive condition, characterized by severe secretory diarrhea that produces a permanent intestinal failure and dependency on parenteral nutrition. It usually begins in the neonatal period, and the only treatment at present is intestinal transplantation. PATIENTS AND METHODS: A retrospective review was conducted on 6 patients (three males and three females) diagnosed with microvillous inclusion disease between 1998 and 2013. RESULTS: All debuted in the first month of life, with a median age of three days (range, 3-30 days), and had secretory diarrhea dependent on parenteral nutrition, with fasting fecal volume of 150-200ml/kg/day. Light microscopy of duodenal biopsy samples showed varying degrees of villous atrophy without cryptic hyperplasia, accumulation of PAS positive material in the cytoplasm of enterocytes brush border, and anti-CD10 immunostaining was suggestive of intracytoplasmic inclusions. Diagnostic confirmation was performed with electron microscopy. Two of them had a genetic study, and showed mutations in MYO5B gene. Three died and three are alive; two of them with an intestinal transplantation and the third waiting for a multivisceral transplantation.

Mucopolysaccharidoses and mucolipidoses.

The mucopolysaccharidoses (MPS) and mucolipidoses (ML) are progressive storage disorders that share many clinical features varying from facial dysmorphism, bone dysplasia, hepatosplenomegaly, neurological abnormalities, developmental regression, and a reduced life expectancy at the severe end of the clinical spectrum to an almost normal clinical phenotype and life span in patients with more attenuated disease. MPS and ML are transmitted in an autosomal recessive manner, except for the X-linked MPS II (Hunter syndrome). Diagnosis is initially by detecting partially degraded GAG or oligosaccharide in urine and confirmed by specific enzyme assays in serum, leukocytes, or skin fibroblasts. For the majority of disorders treatment is palliative, but there have been important advances in the use of specific enzyme replacement therapy strategies for some MPS disorders and this is an area of very rapid development. In addition, hematopoietic stem cell transplantation (HSCT) can improve outcome in carefully selected patients with MPS (especially MPS IH, Hurler syndrome), but this procedure is associated with significant risk. Gene augmentation/transfer using a variety of vectors has been successful in animal models but has not yet been successfully performed in a human patient with one of these disorders. It is important to remember that prenatal diagnosis is possible for all of these disorders.

Unusual pulmonary findings in mucolipidosis II.

We report undescribed pulmonary findings in a child with mucolipidosis II (ML-II). Children with ML-II bear significant pulmonary morbidity that may include extensive pulmonary fibrosis, persistent hemosiderosis as well as pulmonary airway excrescences as they reach preschool age.

Use of an omega-3 fatty acid-based emulsion in the treatment of parenteral nutrition-induced cholestasis in patients with microvillous inclusion disease.

Microvillous inclusion disease is a congenital intestinal epithelial cell disorder leading to lifelong intestinal failure. In this report, we discuss the use of a fish oil-based lipid emulsion in the treatment of 3 patients with microvillous inclusion disease who developed parenteral nutrition-associated liver disease.

Microvillous inclusion disease: how to improve the prognosis of a severe congenital enterocyte disorder.

BACKGROUND AND OBJECTIVE: Microvillous inclusion disease (MVID) is a rare congenital enterocyte disorder causing severe diarrhea and intestinal failure. The objective of this study was to analyze clinical evolution and the most frequent complications of MVID in children receiving parenteral nutrition (PN) and after small-bowel transplantation (SBTx) with the aim to improve treatment strategies and prognosis. PATIENTS AND METHODS: From 1995 to 2009, 24 patients (16 boys, median follow-up 4.7 years, range: from birth to 23.5 years) with MVID were admitted to our unit. The recorded parameters included growth, neurological development, liver and renal functions, bone disease, and outcome. RESULTS: Almost half of the children were from consanguineous families from the Mediterranean area. All of the patients completely depended on PN. Four children died of PN complications before 4 years of age. Before or without SBTx, growth failure was common (mean height -2.5 standard deviations [SD]), as was developmental delay (12/24), liver (20/22 with fibrosis) or kidney disease (3/23 with moderate renal insufficiency), and osteoporosis (6/24). Thirteen children underwent SBTx (9 isolated, 4 combined with liver Tx) at a median age of 3.5 years. Follow-up after SBTx was 0.4 to 14 years. Patient survival rates were 63% without SBTx and 77% with SBTx. After SBTx, 4 children experienced catch-up growth. CONCLUSIONS: PN in MVID is difficult to manage and requires expertise. Despite improved results in expert centers, the risk of death or irreversible sequelae is higher with PN than after Tx. SBTx, despite being complicated, remains the only hope to improve the quality of life and long-term prognosis of these children.

Mucolipidosis IV in an African American patient with new findings on electron microscopy.

PURPOSE: We report an unusual case of mucolipidosis IV in a patient of African ancestry, with intracytoplasmic inclusions of the corneal endothelium found on electron microscopy. METHOD: Clinical description with light and electron microscopy. RESULTS: We describe a case of mucolipidosis IV diagnosed in a patient of African ancestry after penetrating keratoplasty. Electron microscopic evaluation revealed intracytoplasmic inclusions in both the corneal epithelium and endothelium. CONCLUSION: The diagnosis of mucolipidosis in a patient of African ancestry is unusual, as this genetic disorder is found predominantly in individuals of Jewish descent. Corneal endothelial involvement in mucolipidosis IV has not previously been reported.

Use of the palmaris brevis flap for preventing recurrent median nerve compression in mucolipidosis.

In a patient with severe, recurrent bilateral carpal tunnel syndrome secondary to mucolipidosis, the 'turnover' palmaris brevis flap was used in conjunction with internal neurolysis. The procedure was effective in alleviating symptoms of recurrent carpal tunnel compression in both hands.

[Gingival hypertrophy in I-cell disease (mucolipidosis II). A report of 2 nonfamilial cases. II]. / Ipertrofia gengivale nella I-cell disease (mucolipidosi II). Presentazione di due casi non familiari. Parte II.

Two nonconsanguineous patients affected by I-cell disease (mucolipidosis II) are reported. I-cell disease, an oligosaccharidosis, is characterized by severe psychomotor retardation, marked shortness of stature, coarse facies, gingival enlargement, generalized bone demineralization, periosteal cloaking of long bones visible in early infancy, a rapid deteriorating course, and death from heart failure or bronchopneumonia, usually by the age of 5 years. This disorder is the result of a deficiency of glycoprotein N-acetylglucosaminylphosphotransferase activity, necessary for proper intracellular processing of lysosomal enzymes. Inheritance is autosomal recessive. It received the name I-cell disease because of several granular inclusions in the cytoplasm of cultured fibroblasts and amniotic fluid cells observed under phase contrast microscopy. These granules represent altered lysosomes. The two patients, reported here, had a very marked gingival hypertrophy and, for this reason, were referred to the Oral Pathology Service of Galliera Hospital. A gingivectomy was performed on patient 2 to improve the mastication, but few months later gingival hypertrophy reappeared.

Bone marrow transplantation for genetic and metabolic disorders.

Bone marrow transplantation (BMT) was primarily used for the treatment of hematologic malignancies and aplastic anemias. BMT has been successfully applied as curative treatment in a series of lethal congenital disorders but among more than 1000 inherited metabolic diseases only 20 of them can be corrected by transplantation. The inborn error must be expressed in the stem cells. The genetic disorders that can be cured include congenital immune deficiencies, osteopetrosis, and congenital lysosomal storage diseases, mucopolysaccharidosis and lipidosis. BMT with an HLA matched donor is successful in 60% of patients with severe combined immune deficiency and Wiskott Aldrich syndrome. Results are good in osteopetrosis if BMT is performed early. Encouraging results have been reported in Hurler disease and in Gaucher disease.

Improvement of tear lysosomal enzyme levels after treatment with bone marrow transplantation in a patient with I-cell disease.

We examined the lysosomal enzyme levels in tear fluids from a patient with I-cell disease after treatment by bone marrow transplantation. Acid phosphatase, beta-D-glucuronidase, N-acetyl-beta-D-glucosaminidase, alpha-L-fucosidase and alpha-D-mannosidase activities were reduced to normal or nearly normal levels after the treatment. We believe that the measurement of tear enzyme levels in I-cell disease is useful for knowing the efficacy of the bone marrow transplantation.