Acanthosis nigricans as a diagnostic clue for familial partial lipodystrophy type 2: a case report with review of literature on Japanese cases

Familial partial lipodystrophy (FPLD) is a rare inherited disorder characterized by limb adipose tissue atrophy and metabolic abnormalities, including severe insulin resistance. However, diagnosis is often delayed because the characteristic physique can be difficult to recognize without a high index of suspicion. We present the case of a 19-year-old Japanese woman diagnosed with FPLD type 2 (FPLD2). She had a history of irregular menses and hirsutism since adolescence. The FPLD2 diagnosis was prompted by her concerns about axillary and inguinal pigmentation. Her mother’s online search first suggested acanthosis nigricans (AN). After including “muscular limb” as an additional search term, they suspected lipodystrophy, prompting a consultation with an endocrinologist. Clinical examination revealed impaired glucose tolerance, severe insulin resistance, dyslipidemia, fatty liver, and polycystic ovary syndrome. Genetic testing identified a heterozygous LMNA p.R482Q variant, confirming the diagnosis. This case demonstrates that AN, a skin manifestation of insulin resistance, is an important diagnostic clue for FPLD. Although women with FPLD frequently present with menstrual irregularities and hirsutism in their late teens, their insulin levels are rarely measured before diabetes onset. Consequently, the underlying severe insulin resistance is frequently overlooked. Although reported cases of FPLD2 in Japan are limited, many cases may remain undiagnosed. Therefore, clinicians should examine the friction-prone areas in non-severely obese individuals with metabolic or menstrual irregularities. The absence of AN does not rule out insulin resistance. Therefore, even without AN, the presence of other features of insulin resistance warrant consideration of FPLD and careful evaluation for limb fat loss, facilitating early diagnosis.