Thread by @vikkypaedia

Folks....!
A 4 month -old girl infant
▶️of consanguineous parents
▶️one of her brothers died at the age of 2 mth due to #SIDS with the other brothers being normal; presents with
▶️Dysmorphic features
▶️growth faltering
#MedTwitter #FOAMed #TipsForNewDocs

▶️Delivered by LSCS section at 38 wk gest due to intrauterine growth retardation.
▶️birth weight 1240 g, length was 37.3 cm , head circumference was 30.5 cm
▶️At the age of 12 days, she was admitted for suspected sepsis for a week and discharged in good general condition.

▶️Now at 4 months, severely growth retarded with normal mentality,
▶️weight 2.5 kg, length 47 cm ; head circumference 36 cm (all growth parameters below the 3rd centile).

Exam:
elfin facies
protruding deformed👂
big widely placed👀
depressed👃bridge
overgrown gum
prominent nipples
umbilical hernia
abd distension
dark skin (a. nigricans)
lipodystrophy
wrinkled hairy loose skin
wrinkled loose skin
abn body proportions with very big feet &palm.

▶️genitalia showed a big clitoris without palpable gonads
▶️Cardiac auscultation revealed a murmur suggestive of VSD which was confirmed by echocardiography.

Investigations :
▶️hypoglycemia with fasting blood glucose ranging between 33 mg% to 46 mg%, and
▶️high levels of postprandial glucose ranging between 299 mg% and 476 mg% in repeated measurement,

▶️insulin & C-peptide levels ⏫
▶️FT4 ,TSH level - normal
▶️ACTH, cortisol, & 17 hydroxyprogesterone - normal.
▶️basal GH level ⏫
▶️on the other hand, the level of IGF‐1 was ⏬& insulin-like growth factor-binding protein three was ⏬

This child has a combination of a variety of physical features &metabolic symptoms, such as
growth retardation
hirsutism,
acanthosis nigricans,
lipoatrophy,
clitoromegaly,
fasting hypoglycemia postprandial hyperglycemia, insulin resistance, and
hyperinsulinemia

DDs of the disorders that share mutations in the INSR gene, include
▶️type-A insulin resistance syndrome
▶️Rabson Mendenhall syndrome,and
▶️Donahue syndrome,DS (the case here)

▶️They represent a continuum or spectrum of diseases.
▶️Rabson-Mendenhall syndrome have a mod form in severity & may survive to adult age
▶️type-A insulin resistance syndrome affects pubertal girls & present with hyperandrogenism, acanthosis nigricans,& hyperinsulinism

▶️This case has marked hyperglycemia, profound hyperinsulinemia assd with hypoglycemia.
▶️This indicates defective insulin secretion & func at the same time.

▶️Hypoglycemia in DS may be d/t an accelerated fasting state secondary to insulin resistance, scarce stores of glycogen, & deficient gluconeogenesis
▶️The typical cardiac affection in DS is hypertrophic cardiomyopathy which is attributed to severe hyperinsulinism

▶️the case in the vignette; Donohue syndrome (DS) is a very rare genetically encoded, autosomal recessive disorder linked with severe insulin-resistant diabetes.
▶️Was treated with high-dose insulin & freq nasogastric formula milk feeding to achieve reasonable glycemic control.

▶️A limited therapeutic option is available so far for this syndrome.
▶️Also the use of recombinant human insulin-like growth factor-1 (rhIGF-1) may be clinically useful, effective and may result in an ⏫ lifespan
Source: 10.1515/crpm-2021-0087