Congenital generalized lipodystrophy Type 2 (BSCL2; OMIM #269700) presenting with muscular hypertrophy and chronic steatorrhea in a Pakistani child: a pediatric case report confirmed by real-time PCR gene analysis

Abstract Background Congenital generalized lipodystrophy (CGL), or Berardinelli-Seip syndrome, is a rare autosomal recessive condition with near-complete lack of metabolically functional adipocytes since birth or in early infancy, leading to severe metabolic complications. The prevalence of CGL is less than 1 case per million births, and it occurs in four genetic types (CGL1-CGL4). CGL type 2 (mutations in the BSCL2 gene; OMIM #269700) is the most common subtype (70–80% of cases), and has the most severe metabolic complications. Timely diagnosis is essential to avoid potentially fatal complications by early metabolic surveillance and treatment. Case presentation A 5.5-year-old Pakistani male child was referred for a muscular bodybuilder-like look since 24 months of age, chronic steatorrhea (4–5 times a day, aggravated by fat intake), hyperphagia, and poor growth. His birth was normal at term through a normal vaginal delivery and with normal weight and milestones. His family history was negative for lipodystrophy and metabolic disease. His weight (16 kg) and height (105 cm) were below 10th percentile with a BMI of 14.5 kg/m² (< 5th percentile). He had diffuse muscular hypertrophy with a complete loss of subcutaneous fat, visible veins, coarse face with facial lipoatrophy, abdominal distension with hepatomegaly (4 cm below the right costal margin, span 12 cm) and an everted umbilicus. There were no signs of acanthosis nigricans, xanthomas, hirsutism or splenomegaly. Real-Time PCR (RT-PCR) gene analysis confirmed CGL Type 2: BSCL2 exons 4 and 7 were detected; AGPAT2, CAV1, and PTRF were not detected. Both parents confirmed as carriers; all four siblings are unaffected (three heterozygous carriers, one non-carrier). Routine investigations showed macrocytic anaemia (Hb 10 g/dL, MCV 110.8 fL), raised transaminases (ALT 71 U/L, AST 97 U/L), grossly raised IgG (2727.98 mg/dL) and low IgA (4.39 mg/dL). Ultrasonography showed hepatic steatosis. Creatine phosphokinase (103 U/L) was normal, ruling out primary muscular dystrophy. IgA anti-tissue transglutaminase was negative, so coeliac disease was excluded. Hepatitis B, C and HIV were negative. Rickets and skeletal dysplasia were ruled out by a skeletal survey. Fasting triglycerides 862 mg/dL, serum leptin 0.4 ng/mL, and HOMA-IR 10.4 confirmed severe metabolic dysfunction characteristic of CGL2. Based on clinical and biochemical findings, RT-PCR confirmed the diagnosis of CGL type 2 (BSCL2; OMIM #269700) was made. A low-fat diet (20–30% of total energy) with medium-chain triglyceride supplementation, metabolic control and genetic counselling was started. Conclusions This RT-PCR confirmed case of CGL2 demonstrates the triad of CGL: diffuse lipoatrophy with muscular hypertrophy, hepatomegaly secondary to steatosis, and steatorrhoea, with poor growth. To our knowledge, this is the first RT-PCR confirmed CGL2 case reported from Pakistan. Early diagnosis of this rare condition is important to start life-changing metabolic interventions that include dietary restriction, metreleptin replacement and treatment of dyslipidaemia, which may dramatically impact the disease progression and outcome in childhood.