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01

Male
Youngest of four children of healthy, consanguineous
parents
Born at term, without complications
No remarkable medical history during his first year of life

At the age of 1 year:

At the age of 2 years:

Negative tests for:

Diarrhoea
Failure to gain weight

Abdominal ultrasound demonstrated
nephrocalcinosis.

 Hospitalized with: 

Other laboratory investigations:
Bilirubin, ALT, AST, GGT, thrombocyte count normal.

Fever and macrohematuria
Microcytic anaemia (haemoglobin 7.6 g/dL)
Hypoalbuminaemia (albumin 3.2 g/dL)

Celiac serology
Sweat test (normal)
Stool elastase (normal)
Upper endoscopy including
intestinal histology (normal)

Normalisation of hyperbilirubinaemia and INR
Slight elevation of liver enzymes without
hyperbilirubinaemia observed on repeated
tests (ALT 50 IU/ml, AST 50 IU/ml,
normal GGT 12 IU/ml).

Discharged with fat-soluble vitamin
supplementation (A, D, E, K).
During ambulatory follow-up:

Admitted for further investigations
and follow-up:

Diagnosis of 3β-HSD deficiency

Laboratory investigations:

Further investigations

Weight and height were on the 10th percentiles
Physical/neurological examinations were normal

Suspicion of a defect in BA synthesis due to liver
damage and fat malabsorption with normal
GGT and serum bile acids levels

Abdominal ultrasound demonstrated hepatomegaly and
periportal fibrosis
Liver autoimmune workup, alpha-1-antitrypsin blood levels
and phenotype, as well as an infection workup were normal
Upper gastrointestinal endoscopy, including intestinal biopsies,
ruled out villous atrophy/microvillus inclusion disease,
chylomicron retention disease or intestinal lymphangiectasia
Liver biopsy: active liver disease with bridging fibrosis and an
ongoing destructive process

Analysis of urinary bile acid metabolites: typical
for 3β-hydroxy-Δ⁵-C₂₇-steroid dehydrogenase
deficiency
Confirmation by HSD3B7 gene sequencing.

02

Failure to gain weight
and height

Hepatomegaly

Diarrhea
Fever
Macrohematuria
Microcytic anemia

Elevated INR
Hypoalbuminaemia

Slightly elevated liver enzymes
without bilirubinaemia

Consanguineous parents

Active liver disease: fibrosis and
ongoing destructive process

Physicians should suspect bile acids synthesis defects in the context of fat malabsorption even in the absence of overt cholestasis, especially in
the presence of normal serum bile acids.

Fat-soluble vitamin deficiency

Normal GGT
Normal total serum bile acids

03